Session 8: Acute Inflammation

Session 8: Acute Inflammation

• Alex Simon

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Learning tasks

Learning tasks

At the end of this session, students are expected to be able to:

Identify hallmarks of acute inflammation.

Identify stimuli for acute inflammation.

Explain cardinal signs of acute inflammation.

Explain components of acute inflammation.

Explain morphological patterns of acute inflammation.

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Introduction

Introduction

Acute inflammation is a rapid response to injury or microbes or foreign bodies to vascularized tissue.

The acute inflammatory response rapidly delivers leukocytes (neutrophils) and plasma proteins to sites of injury.

Once there, leukocytes clear the invaders and begin the process of digesting and getting rid of necrotic tissues.

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Hallmarks of Acute inflammation

Hallmarks of Acute inflammation

These are main features of acute inflammation.

These include

Exudation of fluids and plasma proteins at the site of injury.

Emigration of polymorphonuclear neutrophils to the site of injury.

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Stimuli for Acute inflammation

Stimuli for Acute inflammation

Acute inflammatory reactions may be triggered by a variety of stimuli

Infections.

Trauma.

Tissue necrosis.

Foreign bodies.

Immune reactions against environmental substances or against “self” tissues.

All inflammatory reactions from these stimuli have the same basic features.

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Cardinal signs of Acute inflammation

Cardinal signs of Acute inflammation

These are clinical features/signs seen mainly in acute inflammation.

These are external manifestations of inflammation.

Redness (rubor)

Heat (calor)

Swelling (tumor)

Pain (dolor)

Loss of function (functio laesa)

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Cardinal signs of acute inflammation cont…

Cardinal signs of acute inflammation cont…

Redness (rubor)

Due to local increase in blood flow after dilation of small blood vessels within damaged tissue.

Hotness/Heat (calor)

It results from increased blood flow due to regional vascular dilation.

Swelling (tumor)

Due to accumulation of fluid in the extravascular space from increased vascular permeability.

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Cardinal signs of acute inflammation cont…

Cardinal signs of acute inflammation cont…

Pain/tenderness (dolor)

Due to direct nerve injury.

Stretching & destruction of tissues due to inflammatory edema.

Chemical mediators: bradykinins, prostaglandins and serotonin induce pain.

Loss of function (functio laesa)

Due to temporary or permanent tissue damage.

Inflamed area is inhibited by pain while severe swelling may physically immobilize the tissue.

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Major components of Acute Inflammation

Major components of Acute Inflammation

These are principal reactions of acute inflammation.

Acute inflammation has two (2) major components

Vascular changes.

Cellular events.

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Vascular changes

Vascular changes

The main vascular reactions of acute inflammation are

Transient vasoconstriction.

Arteriolar vasodilation results in an increased blood flow.

Increased vascular permeability, both designed to bring blood cells and proteins to sites of infection or injury.

Both (ii) and (iii) above are designed to bring blood cells and proteins to sites of infection or injury.

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Transient vasoconstriction

Transient vasoconstriction

Diameter of blood vessels decrease immediately after an insult.

This is a very short event lasting for a few seconds.

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Arteriolar vasodilatation

Arteriolar vasodilatation

This is a predominant feature in acute inflammation.

Vasodilatation of arterioles and venules resulting in increased blood flow.

This results to increased blood flow and engorgement of the down-stream capillary beds.

This vascular expansion is the cause of the redness (erythema) and warmth characteristically seen in acute inflammation.

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Increase vascular permeability

Increase vascular permeability

Progressive vasodilatation, in turn, may elevate the local hydrostatic pressure.

The microvasculature becomes more permeable, protein-rich fluid moves into extravascular tissues.

The process called exudation.

The protein-rich fluid which is now found in the extravascular space is called exudate.

The presence of the exudates clinically appears as swelling.

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Increase vascular permeability cont…

Increase vascular permeability cont…

Exudation causes the red cells in the flowing blood to become more concentrated, thereby increasing blood viscosity and slowing the circulation called stasis.

As stasis develops, leukocytes (principally neutrophils) begin to accumulate along the vascular endothelial surface—a process called margination.

This is the first step of neutrophils through the vascular wall into the interstitial tissue.

This process is known as emigration.

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Exudation

Exudation

Advantages of Exudation

Dilute toxins in the area of inflammation.

Globulins are protective antibodies.

Fibrin helps in limiting inflammation and assists wound healing.

Components of exudates include

Water.

Proteins: Immunoglobins, albumins, fibrinogen.

Hormones.

Natural antibacterial opsonins.

Cells: Leucocytes.

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Exudate vs Transudate

Exudate vs Transudate

Parameter

EXUDATE

TRANSUDATE

Definition

Oedema associated with increased vascular permeability

Filtrate of blood plasma without endothelial permeability

Character

Inflammatory edema

Non inflammatory edema

Protein

High (2.5-3.5g/dl) contains high fibrinogen

Low (less than 1g/dl) mainly albumin, low fibrinogen

Specific gravity

High (more than 1.018)

Low (less than 1.015)

pH

Less than 7.3

More than 7.3

Cells

Many cells, inflammatory as well as parenchymal

Few cells, mainly mesothelial cells and cell debris

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Mechanisms that contribute to increased vascular permeability

Mechanisms that contribute to increased vascular permeability

Contraction of endothelial cells (most common).

Retraction of endothelial cells.

Direct injury to endothelial cells.

Endothelial injury mediated by leucocytes.

Leakiness in neovascularization.

Increased transcytosis of proteins.

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Cellular events

Cellular events

Cellular events involve three (3) important steps

Leucocytes recruitment.

Leucocytes activation.

Phagocytosis.

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Leukocytes recruitment

Leukocytes recruitment

The sequence of events in the recruitment of leukocytes from the vascular lumen to the extravascular space consists of:

Margination and rolling along the vessel wall.

Firm adhesion to the endothelium.

Transmigration between endothelial cells.

Migration in interstitial tissues toward a chemotactic stimulus.

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Margination

Margination

It is a process whereby leukocytes accumulate at the periphery of blood vessels.

This occur because leukocytes are pushed out of the central axial column and interact with lining endothelial cells.

It is a peripheral positioning of white cells along the endothelial cells.

The appearance seen when endothelium virtually lined by white cells is called pavementing.

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Rolling

Rolling

Endothelial cells are activated by cytokines and other mediators produced locally, then express adhesion molecules to which the leukocytes attach loosely.

These leukocytes bind and detach and thus begin to tumble on the endothelial surface.

Thus weak and transient interactions (binding) involved in rolling are mediated by the selectins.

E-selectin

P-selectin

L-selectin.

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Adhesion

Adhesion

The rolling leukocytes will attach firm to endothelial surfaces.

This process is mediated by adhesion molecules called integrins.

Integrins mediate adhesion of leukocytes to endothelium.

Integrins are expressed on leukocyte cell surfaces membrane interacting with their ligands on endothelial cells.

Becomes active until the leukocytes are activated by chemokines.

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Transmigration

Transmigration

Leukocytes migrate through the vessel wall (between endothelial cells) primarily by squeezing between cells at intercellular junctions.

This is by pseudopodia (diapedesis).

Migration of leukocytes is driven by chemokines and platelet endothelial cell adhesion molecule-1 (PECAM-1).

Leukocytes secrete collagenases that enable them to pass through the vascular basement membrane.

The basement membrane is disrupted and resealed thereafter immediately.

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Chemotaxis

Chemotaxis

Leukocytes move toward sites of infection or injury from the blood vessel along a chemical gradient (including bacteria and cellular debris) by a process called chemotaxis.

Substances that can be chemotactic for leukocytes

Bacterial products.

Chemokines.

Complement 5 (C5).

Leukotriene B4 (LTB4).

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Leukocyte Activation

Leukocyte Activation

Once leukocytes have been recruited to the site of infection or tissue necrosis, they must be activated to perform their functions.

Stimuli for activation include

Microbes.

Products of necrotic cells.

Several chemical mediators like Leukotriene B4.

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Phagocytosis

Phagocytosis

It is the process of engulfment and internalization of particulate material (includes invading microorganisms, damaged cells, and tissue debris) by specialized cells (phagocytes).

These phagocytic cells include

Polymorphonuclear leukocytes (particularly neutrophils).

Circulating monocytes.

Tissue macrophages.

Dendritic cells.

Mast cells.

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Phagocytosis cont…

Phagocytosis cont…

Phagocytosis consists of three (3) steps

Recognition and attachment of the particle to the ingesting leukocyte.

Engulfment, with subsequent formation of a phagocytic vacuole.

Killing and degradation of the ingested material.

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Recognition and attachment

Recognition and attachment

Leukocytes bind and ingest most microorganisms and dead cells by means of specific surface receptors.

Some of these receptors recognize components of the microbes and dead cells.

Other receptors recognize host proteins, called opsonins, that coat microbes and target them for phagocytosis (the process called opsonization).

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Engulfment

Engulfment

Binding of opsonized particles to these receptors triggers engulfment and induces cellular activation that enhances degradation of ingested microbes.

In engulfment, pseudopods are extended around the object, eventually forming a phagocytic vacuole.

The membrane of the vacuole then fuses with the membrane of a lysosomal granule forming phagolysosome.

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Killing and degradation of the ingested microbes

Killing and degradation of the ingested microbes

There are two (2) forms of bacterial killing

Oxygen dependent mechanism

By reactive oxygen species.

Oxygen-independent mechanism

By lysosomal enzymes.

Nitric oxide.

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Morphological patterns of acute inflammation

Morphological patterns of acute inflammation

There are three (3) main patterns

Serous inflammation.

Fibrinous inflammation.

Suppurative (purulent) inflammation.

Other patterns are

Ulceration.

Catarrhal inflammation.

Pseudomembranous inflammation.

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Serous inflammation

Serous inflammation

Characterized by the outpouring of a watery, relatively protein-poor fluid.

Derives either from the plasma or from the secretions of mesothelial cells lining the peritoneal, pleural, and pericardial cavities.

Example: Skin blister resulting from a burn or viral infection.

Fluid in a serous cavity is called an effusion.

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Fibrinous inflammation

Fibrinous inflammation

Resulting from vascular permeability that allows fibrinogen to pass the endothelial barrier.

Histologically, the accumulated extravascular fibrin.

A fibrinous exudate is seen in the lining of meninges, pericardium, and pleura.

Course of fibrinous inflammation include

Resolution by fibrinolysis.

Scar formation when the exudates get organized.

Fibrous strand formation.

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Suppurative (purulent) inflammation

Suppurative (purulent) inflammation

It is manifested by the collection of large amounts of purulent exudate (pus) as seen in abscess and cellulitis.

Pus consist of

A large number of living or dead leukocytes (pus cells)- Neutrophils.

Necrotic tissue debris.

Living and dead bacteria.

Edema fluid.

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Ulceration

Ulceration

An ulcer is a local defect of the surface of an organ or tissue that is produced by necrosis of cells and sloughing (shedding) of necrotic and inflammatory tissue.

Ulcers are most commonly encountered in

The mucosa of the mouth, stomach, intestines, or genitourinary tract.

The subcutaneous tissues of the lower extremities in older persons who have circulatory disturbances.

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Catarrhal inflammation

Catarrhal inflammation

This is a mild and superficial inflammation of the mucous membrane.

It is commonly seen in the upper respiratory tract following viral infections where mucous secreting glands are present in large numbers, e.g. Rhinitis.

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Pseudomembranous inflammation

Pseudomembranous inflammation

Form a false (pseudo) membrane which forms a white or colored layer over the surface of inflamed mucosa.

Fibrinogen, the necrotic epithelium, the neutrophilic polymorphs, red blood cells, bacteria and tissue debris form the pseudo membrane.

Seen in dipthetric and Clostridium difficille infection.

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Key points

Key points

Exudation and neutrophils are hallmark of acute inflammation.

Neutrophils are predominant white blood cells in acute inflammation.

The major components of acute inflammation are vascular changes and cellular events.

Arteriolar vasodilation and increase vascular permeability are the main vascular reactions of acute inflammation.

Morphologic patterns of acute inflammation are often associated with different etiology and clinical situations.

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Evaluation

Evaluation

Explain pathophysiology of the cardinal sign of acute inflammation.

Explain sequential events involved in leukocytes recruitment during cellular responses of acute inflammation.

Explain three (3) processes of phagocytosis.

Differentiate between serous inflammation and fibrinous inflammation.

Enumerate two (2) outcomes of suppurative inflammation.

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References

References

Bezabeh M.; Tesfaye A.; Ergicho B. et al (2004): General pathology lecture notes for Health Sciences students. Ethiopia Public Health Training Initiative. Pg. 25-33.

Kumar V.; Abbas A. K.; Aster J. C.;(2013): Robbins and Contran Pathologic Basis of Disease (9th Ed.) Elsevier Saunders, China. Pg. 31-38.

Mohan H.;(2010): Text book of Pathology (6th Ed.) Jaypee Brothers Medical Publishers, India. Pg.130- 136.

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